Azelastine is a phthalazinone derivative having the following structural formula: ##STR1##
The chemical designation of azelastine is 4-(4-chlorobenzyl)-2-(perhydro-1 methylazepine-4-yl)-1-(2H) phthalazinone. Azelastine is particularly useful in asthma prophylaxis. Azelastine also has anti-allergic and antihistaminic properties, see German Patent No. 21 64 058.
Azelastine dissolves to the extent of 0.005% in water at 20.degree. C.
Previously used salts of azelastine display the following solubility in water at 20.degree. C.:
hydrochloride 1% PA0 embonate 0.0015% PA0 acetate: 116.degree.-118.degree. C. gluconate: 61.degree.-66.degree. C. PA0 lactate: 139.degree.-140.degree. C. malate: 154.degree.-155.degree. C. PA0 azelastine gluconate: 0.1-50, preferably 1-50 percent by weight PA0 azelastine acetate: 0.1-20, preferably 1-20 percent by weight PA0 azelastine lactate: 0.1-20, preferably 1-20 percent by weight PA0 azelastine malate: 0.1-5, preferably 1-3 percent by weight
Other salts of azelastine have the following solubilities:
______________________________________ succinate phosphate solubility maleate in water at 20.degree. C. citrate ca. 1% methane sulphonate fumarate toluene sulphonate under 1% benzene sulphonate tartrate ______________________________________
The solubilities quoted, as well as the marked dependence of solubility on temperature, result in the salts not being suitable for the preparation of pharmaceutical formulations having a higher content of dissolved azelastine. The preparation of locally applied formulations, in particular those with a limited water content (for example emulsion ointments and creams as well as gels) call for the availability of more highly concentrated aqueous solutions in order to provide the required amounts of active substances to the skin or mucous membrane.